PAPER
Synthesis of the 4,10-Dihydro-3H-pyridazino[1,6-b]isoquinolin-10-one System
2213
MS (EI, 70 eV): m/z (%) = 373/371 (6/6) [M+ + 1], 372/370 (21/21)
[M+], 357 (54), 355 (100), 354 (96), 353 (41), 342 (34), 340 (34),
327 (17), 325 (19), 232 (13).
MS (EI, 70 eV): m/z (%) = 327/325 (3/10) [M+ + 1], 326/324 (15/
45) [M+], 284 (10), 283 (37), 282 (22), 281 (100), 255 (11), 253
(22).
Anal. Calcd for C18H15BrN2O2: C, 58.24; H, 4.07. Found: C, 58.31;
H, 4.11.
Anal. Calcd for C18H13ClN2O2: C, 66.57; H, 4.03. Found: C, 66.50;
H, 4.08.
7-Amino-11-bromo-2,4-dimethyl-6,7-dihydro-8H-fu-
ro[2¢,3¢:3,4]cyclohepta[1,2-c]isoquinolin-8-one (9f)
Yield: 690 mg (62%); pale yellow needles; mp 255 °C.
8-Bromo-2-methyl-5-(5-methyl-2-furyl)-10H-pyridazino[1,6-
b]isoquinolin-10-one (13c)
Yield: 221 mg (60%); orange needles; mp 236–237 °C.
IR (KBr): 3288, 3206, 1627, 1570, 1003, 926, 829, 773 cm–1.
IR (KBr): 1680, 1516, 1466, 1333, 1297, 1023, 876, 822, 791 cm–1.
1H NMR (600 MHz, DMSO-d6): d = 1.85–2.70 (br m, 1 H, CH2),
1.99 (s, 3 H, CH3), 2.47 (s, 3 H, CH3), 3.95–4.80 (br m, 1 H, CH2),
5.43–5.45 (m, 1 H, = CH), 6.02 (s, 2 H, NH2), 6.54 (s, 1 H, HFur),
7.68 (dd, J = 1.9, 8.6 Hz, 1 H, HAr), 8.22 (d, J = 8.6 Hz, 1 H, HAr),
8.53 (d, J = 1.9 Hz, 1 H, HAr).
1H NMR (600 MHz, DMSO-d6): d = 2.37 (s, 3 H, CH3), 2.46 (s, 3
H, CH3), 6.36 (d, J = 3.0 Hz, 1 H, 4-HFur), 6.61 (d, J = 3.0 Hz, 1 H,
3-HFur), 6.99 (d, J = 9.6 Hz, 1 H, HPyr), 7.48 (d, J = 8.4 Hz, 1 H,
HAr), 7.61 (d, J = 9.6 Hz, 1 H, HPyr), 7.95 (dd, J = 2.4, 8.4 Hz, 1 H,
HAr), 8.56 (d, J = 2.4 Hz, 1 H, HAr).
13C NMR (150 MHz, DMSO-d6): d = 13.5, 19.7, 27.9, 102.8, 105.9,
116.2, 121.5, 126.0, 126.1, 126.7, 129.0, 129.8, 131.3, 134.2, 137.7,
147.2, 150.4, 159.7.
13C NMR (150 MHz, DMSO-d6): d = 13.5, 21.7, 102.2, 107.4,
114.0, 119.2, 122.3, 123.6, 127.0, 129.8, 131.5, 133.8, 134.0, 135.8,
144.2, 152.9, 153.0, 156.7.
MS (EI, 70 eV): m/z (%) = 373/ 371 (5/5) [M+ + 1], 372/370 (21/19)
[M+], 357 (42), 356 (97), 355 (100), 354 (66), 342 (22), 340 (27),
327 (36), 325 (37), 233 (15), 149 (14).
MS (EI, 70 eV): m/z (%) = 371/369 (10/13) [M+ + 1], 370/368 (43/
48) [M+], 328/326 (31/33), 327/325 (100/100), 299 (20), 297 (21),
217 (13), 218 (13), 190 (20), 189 (21), 150 (18).
Anal. Calcd for C18H15BrN2O2: C, 58.24; H, 4.07. Found: C, 58.18;
H, 4.01.
Anal. Calcd for C18H13BrN2O2: C, 58.56; H, 3.55. Found: C, 58.48;
H, 3.51.
Compounds 13a–c,e,f; General Procedure
7-Chloro-2-methyl-5-(5-methyl-2-furyl)-10H-pyridazino[1,6-
b]isoquinolin-10-one (13e)
Yield: 189 mg (58%); orange needles; mp 233–234 °C.
A mixture of the appropriate compound 8 (1 mmol) and DDQ (1.1
mmol) in benzene (8 mL) was refluxed for 5–7 min (TLC). The sus-
pension thus obtained was poured into H2O (50 mL) and extracted
with EtOAc (3 × 30 mL). The extract was evaporated and the resi-
due was purified by column chromatography (EtOAc–PE, 1:2). The
product was recrystallized (EtOAc–PE).
IR (KBr): 1676, 1596, 1524, 1464, 1332, 1292, 1020, 956, 872, 832,
788 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 2.38 (s, 3 H, CH3), 2.45 (s, 3
H, CH3), 6.35 (d, J = 3.1 Hz, 1 H, 4-HFur), 6.61 (d, J = 3.1 Hz, 1 H,
3-HFur), 6.98 (d, J = 9.6 Hz, 1 H, HPyr), 7.44 (d, J = 2.1 Hz, 1 H,
HAr), 7.56 (d, J = 9.6 Hz, 1 H, HPyr), 7.58 (dd, J = 2.1, 8.7 Hz, 1 H,
HAr), 8.47 (d, J = 8.7 Hz, 1 H, HAr).
2-Methyl-5-(5-methyl-2-furyl)-10H-pyridazino[1,6-b]isoquino-
lin-10-one (13a)
Yield: 171 mg (59%); orange needles; mp 181–182 °C.
13C NMR (75 MHz, DMSO-d6): d = 13.1, 21.4, 101.0, 107.2, 113.8,
120.6, 122.4, 122.8, 126.3, 130.2, 131.1, 134.5, 136.3, 137.9, 143.9,
152.4, 152.8, 157.0.
MS (EI, 70 eV): m/z (%) = 327/325 (4/6) [M+ + 1], 326/324 [M+]
(17/44), 284/282 (10/26), 283/281 (39/100), 255 (17), 253 (25), 177
(17), 149 (17).
IR (KBr): 1683, 1605, 1526, 1473, 1299, 824, 802, 773, 693 cm–1.
1H NMR (600 MHz, DMSO-d6): d = 2.37 (s, 3 H, CH3), 2.43 (s, 3
H, CH3), 6.35 (d, J = 3.0 Hz, 1 H, 4-HFur), 6.59 (d, J = 3.0 Hz, 1 H,
3-HFur), 6.92 (d, J = 9.6 Hz, 1 H, HPyr), 7.52–7.53 (m, 1 H, HAr), 7.58
(d, J = 9.6 Hz, 1 H, HPyr), 7.59–7.62 (m, 1 H, HAr), 7.79–7.81 (m, 1
H, HAr), 8.48–8.49 (m, 1 H, HAr).
13C NMR (150 MHz, DMSO-d6): d = 13.5, 21.7, 102.5, 107.3,
113.7, 121.8, 122.3, 124.5, 126.5, 127.9, 131.5, 132.9, 133.3, 135.2,
144.7, 152.4, 152.7, 157.7.
MS (EI, 70 eV): m/z (%) = 291 (15) [M+ + 1], 290 (51) [M+], 248
(31), 247 (100), 219 (16), 190 (12), 152 (9), 151 (10).
Anal. Calcd for C18H13ClN2O2: C, 66.57; H, 4.03. Found: C, 66.64;
H, 4.10.
7-Bromo-2-methyl-5-(5-methyl-2-furyl)-10H-pyridazino[1,6-
b]isoquinolin-10-one (13f)
Yield: 210 mg (57%); orange needles; mp 240 °C (sublimed).
Anal. Calcd for C18H14N2O2: C, 74.47; H, 4.86. Found: C, 74.55; H,
4.90.
IR (KBr): 1672, 1592, 1520, 1460, 1328, 1216, 872, 784 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 2.38 (s, 3 H, CH3), 2.45 (s, 3
H, CH3), 6.37 (d, J = 3.0 Hz, 1 H, 4-HFur), 6.64 (d, J = 3.0 Hz, 1 H,
3-HFur), 7.00 (d, J = 9.6 Hz, 1 H, HPyr), 7.57 (d, J = 9.6 Hz, 1 H,
HPyr), 7.59 (d, J = 1.8 Hz, 1 H, HAr), 7.74 (dd, J = 1.8, 8.4 Hz, 1 H,
HAr), 8.38 (d, J = 8.4 Hz, 1 H, HAr).
13C NMR (75 MHz, DMSO-d6): d = 13.5, 21.8, 101.2, 107.5, 114.1,
121.0, 122.8, 126.2, 127.4, 129.3, 130.5, 131.5, 134.7, 136.6, 144.0,
152.8, 153.1, 157.4.
8-Chloro-2-methyl-5-(5-methyl-2-furyl)-10H-pyridazino[1,6-
b]isoquinolin-10-one (13b)
Yield: 199 mg (61%); orange needles; mp 222–223 °C.
IR (KBr): 1681, 1515, 1469, 1297, 880, 824 cm–1.
1H NMR (600 MHz, DMSO-d6): d = 2.37 (s, 3 H, CH3), 2.45 (s, 3
H, CH3), 6.36 (d, J = 3.0 Hz, 1 H, 4-HFur), 6.61 (d, J = 3.0 Hz, 1 H,
3-HFur), 6.98 (d, J = 9.6 Hz, 1 H, HPyr), 7.56 (d, J = 8.8 Hz, 1 H,
HAr), 7.61 (d, J = 9.6 Hz, 1 H, HPyr), 7.83 (d, J = 2.4, 8.8 Hz, 1 H,
HAr), 8.41 (d, J = 2.4 Hz, 1 H, HAr).
13C NMR (150 MHz, DMSO-d6): d = 13.5, 21.7, 102.2, 107.4,
114.0, 122.3, 123.3, 126.6, 127.0, 130.9, 131.5, 133.1, 133.7, 133.8,
144.3, 152.9, 153.0, 156.8.
MS (EI, 70 eV): m/z (%) = 371/369 (14/22) [M+ + 1], 370/368 (77/
82) [M+], 327/325 (22/20), 326/324 (95/100), 298 (20), 296 (20),
218 (23), 215 (13), 190 (16), 189 (21), 150 (27).
Anal. Calcd for C18H13BrN2O2: C, 58.56; H, 3.55. Found: C, 58.49;
H, 3.51.
Synthesis 2007, No. 14, 2208–2214 © Thieme Stuttgart · New York